151 research outputs found

    Toxic Power: What the Toxics Release Inventory Tells Us About Power Plant Pollution

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    Examines nationwide and state electric utility data to show the quantity and nature of toxic pollutants reported by power plants, and describes the potential health damage they can cause. Suggests ways for reducing toxic power plant pollution

    Electron Spectroscopy and Atomic Force Microscopy Studies of DNA Adsorption on Mica

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    Various methods for the deposition of deoxyribonucleic acid (DNA) molecules on mica are investigated to determine their reproducibility, and to quantify their ability to bind DNA. The use of these deposition methods for sample preparation for biological scanning tunneling microscopy (STM) and atomic force microscopy (AFM) studies is discussed. Auger electron spectroscopy (AES) and electron spectroscopy for chemical analysis (ESCA) were used to investigate the quantity of DNA adsorbed. AFM images of DNA deposited using the methods investigated are presented. The combination of AFM results with AES and ESCA results provides a basic understanding of the deposition techniques studied and illustrates that electron spectroscopy can be a useful addition to studies of this nature

    Beyond immune escape:a variant surface glycoprotein causes suramin resistance in Trypanosoma brucei

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    Suramin is one of the first drugs developed in a medicinal chemistry program (Bayer, 1916), and it is still the treatment of choice for the hemolymphatic stage of African sleeping sickness caused by Trypanosoma brucei rhodesiense. Cellular uptake of suramin occurs by endocytosis, and reverse genetic studies with T. b. brucei have linked downregulation of the endocytic pathway to suramin resistance. Here we show that forward selection for suramin resistance in T. brucei spp. cultures is fast, highly reproducible and linked to antigenic variation. Bloodstream-form trypanosomes are covered by a dense coat of variant surface glycoprotein (VSG), which protects them from their mammalian hosts' immune defenses. Each T. brucei genome contains over 2000 different VSG genes, but only one is expressed at a time. An expression switch to one particular VSG, termed VSGSur , correlated with suramin resistance. Reintroduction of the originally expressed VSG gene in resistant T. brucei restored suramin susceptibility. This is the first report of a link between antigenic variation and drug resistance in African trypanosomes

    Rapid diagnostic test value and implementation in antimicrobial stewardship across low-to-middle and high-income countries: a mixed-methods review

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    Despite technological advancements in infectious disease rapid diagnostic tests (RDTs) and use to direct therapy at the per-patient level, RDT utilisation in antimicrobial stewardship programmes (ASPs) is variable across low-to-middle income and high-income countries. Key insights from a panel of seven infectious disease experts from Colombia, Japan, Nigeria, Thailand, the UK, and the USA, combined with evidence from a literature review, were used to assess the value of RDTs in ASPs. From this, a value framework is proposed which aims to define the benefits of RDT use in ASPs, separate from per-patient benefits. Expert insights highlight that, to realise the value of RDTs within ASPs, effective implementation is key; actionable advice for choosing an RDT is proposed. Experts advocate the inclusion of RDTs in the World Health Organization Model List of essential in vitro diagnostics and in iterative development of national action plans

    Evolution of the solar irradiance during the Holocene

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    Aims. We present a physically consistent reconstruction of the total solar irradiance for the Holocene. Methods. We extend the SATIRE models to estimate the evolution of the total (and partly spectral) solar irradiance over the Holocene. The basic assumption is that the variations of the solar irradiance are due to the evolution of the dark and bright magnetic features on the solar surface. The evolution of the decadally averaged magnetic flux is computed from decadal values of cosmogenic isotope concentrations recorded in natural archives employing a series of physics-based models connecting the processes from the modulation of the cosmic ray flux in the heliosphere to their record in natural archives. We then compute the total solar irradiance (TSI) as a linear combination of the jth and jth + 1 decadal values of the open magnetic flux. Results. Reconstructions of the TSI over the Holocene, each valid for a di_erent paleomagnetic time series, are presented. Our analysis suggests that major sources of uncertainty in the TSI in this model are the heritage of the uncertainty of the TSI since 1610 reconstructed from sunspot data and the uncertainty of the evolution of the Earth's magnetic dipole moment. The analysis of the distribution functions of the reconstructed irradiance for the last 3000 years indicates that the estimates based on the virtual axial dipole moment are significantly lower at earlier times than the reconstructions based on the virtual dipole moment. Conclusions. We present the first physics-based reconstruction of the total solar irradiance over the Holocene, which will be of interest for studies of climate change over the last 11500 years. The reconstruction indicates that the decadally averaged total solar irradiance ranges over approximately 1.5 W/m2 from grand maxima to grand minima

    Concentration Gradients of trans

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    Altered apolipoprotein C expression in association with cognition impairments and hippocampus volume in schizophrenia and bipolar disorder

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    Proteomic analyses facilitate the interpretation of molecular biomarker probes which are very helpful in diagnosing schizophrenia (SZ). In the current study, we attempt to test whether potential differences in plasma protein expressions in SZ and bipolar disorder (BD) are associated with cognitive deficits and their underlying brain structures. Forty-two plasma proteins of 29 SZ patients, 25 BD patients and 93 non-clinical controls were quantified and analysed using multiple reaction monitoring-based triple quadrupole mass spectrometry approach. We also computed group comparisons of protein expressions between patients and controls, and between SZ and BD patients, as well. Potential associations of protein levels with cognitive functioning (psychomotor speed, executive functioning, crystallised intelligence) as well as underlying brain volume in the hippocampus were explored, using bivariate correlation analyses. The main finding of this study was that apolipoprotein expression differed between patients and controls and that these alterations in both disease groups were putatively related to cognitive impairments as well as to hippocampus volumes. However, none of the protein level differences were related to clinical symptom severity. In summary, altered apolipoprotein expression in BD and SZ was linked to cognitive decline and underlying morphological changes in both disorders. Our results suggest that the detection of molecular patterns in association with cognitive performance and its underlying brain morphology is of great importance for understanding of the pathological mechanisms of SZ and BD, as well as for supporting the diagnosis and treatment of both disorders

    Magnetic Coupling in the Quiet Solar Atmosphere

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    Three kinds of magnetic couplings in the quiet solar atmosphere are highlighted and discussed, all fundamentally connected to the Lorentz force. First the coupling of the convecting and overshooting fluid in the surface layers of the Sun with the magnetic field. Here, the plasma motion provides the dominant force, which shapes the magnetic field and drives the surface dynamo. Progress in the understanding of the horizontal magnetic field is summarized and discussed. Second, the coupling between acoustic waves and the magnetic field, in particular the phenomenon of wave conversion and wave refraction. It is described how measurements of wave travel times in the atmosphere can provide information about the topography of the wave conversion zone, i.e., the surface of equal Alfv\'en and sound speed. In quiet regions, this surface separates a highly dynamic magnetic field with fast moving magnetosonic waves and shocks around and above it from the more slowly evolving field of high-beta plasma below it. Third, the magnetic field also couples to the radiation field, which leads to radiative flux channeling and increased anisotropy in the radiation field. It is shown how faculae can be understood in terms of this effect. The article starts with an introduction to the magnetic field of the quiet Sun in the light of new results from the Hinode space observatory and with a brief survey of measurements of the turbulent magnetic field with the help of the Hanle effect.Comment: To appear in "Magnetic Coupling between the Interior and the Atmosphere of the Sun", eds. S.S. Hasan and R.J. Rutten, Astrophysics and Space Science Proceedings, Springer-Verlag, Heidelberg, Berlin, 200

    Fexinidazole – A New Oral Nitroimidazole Drug Candidate Entering Clinical Development for the Treatment of Sleeping Sickness

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    This article describes the preclinical profile of fexinidazole, a new drug candidate with the potential to become a novel, oral, safe and effective short-course treatment for curing both stage 1 and 2 human African trypanosomiasis and replace the old and highly problematic treatment modalities available today. Fexinidazole is orally available and rapidly metabolized in two metabolites having equivalent biological activity to the parent and contributing significantly to the in vivo efficacy in animal models of both stage 1 and 2 HAT. Animal toxicology studies indicate that fexinidazole has an excellent safety profile, with no particular issues identified. Fexinidazole is a 5-nitroimidazole and, whilst it is Ames-positive, it is devoid of any genetic toxicity in mammalian cells and therefore does not pose a genotoxic risk for use in man. Fexinidazole, which was rediscovered through a process of compound mining, is the first new drug candidate for stage 2 HAT having entered clinical trials in thirty years, and has the potential to revolutionize therapy of this fatal disease at a cost that is acceptable in the endemic regions
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